Tetrahydrofuran → 4-Chloro-2-ethyl-3-pyridinamine

HRID 1260458Notes

Reaction equation

HRID 1260458 reaction equation
Br[C:2]1[C:7]([NH2:8])=[C:6]([Cl:9])[CH:5]=[CH:4][N:3]=1.C[Al](C)C.[CH2:14]1COC[CH2:15]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:9][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([CH2:14][CH3:15])[C:7]=1[NH2:8]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 16682925TrimethylaluminumHCID 224762862-Bromo-4-chloropyridin-3-amine

Product 1

HCID 672305994-Chloro-2-ethyl-3-pyridinamine

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

Following a modified synthetic procedure reported in J. Org. Chem. 2006, 71, 7322, a to a stirred solution of 2-bromo-4-chloropyridin-3-amine (prepared as described in US2002/0119982) (1.0 eq.), and Pd(Ph3P)4 (0.05 eq.) in dry THF (0.05M) under argon was added dropwise Me3Al (1.0M in hexane, 2.0 eq.) and the reaction mixture was refluxed for O/N. The volatiles were removed under reduced pressure and the crude product was purified by flash chromatography eluting with 5-100% EtOAc/petroleum ether affording the titled compound as orange oil. 1H NMR (300 MHz, DMSO-d6, 300K) δ 7.67 (1H, d, J=5.2 Hz), 7.11 (1H, d, J=5.2 Hz), 5.26 (2H, br. s), 2.69 (2H, q, J=7.3 Hz), 1.73 (3H, t, J=7.3 Hz). MS (ES) C7H9ClN2 requires: 156, found: 157, 159 (M+H)+.

Workup

  1. temperaturethe reaction mixture was refluxed for O/N
  2. customThe volatiles were removed under reduced pressure
  3. customthe crude product was purified by flash chromatography
  4. washeluting with 5-100% EtOAc/petroleum ether affording the titled compound as orange oil

Sources & evidence

ORD record
ord-039e3351edc142bb866233402de17480
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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